The overall objective of this research program is to continue our efforts directed at the development of efficient procedures for the construction of echinosporin, the hydroxyjatrophones A-C, and related natural products which appear to have significant potential as antitumor agents. We note here that the latter were isolated and their structures elucidated in our laboratory during the 04-06 years of this research program. As new synthetic targets in this area we have selected aphidicolin, and several related, water soluble derivatives and analogs. While aphidicolin is by no means new to the synthetic community, there is now considerable renewed interest in aphidicolin, on the part of the National Cancer Institute and the Pharmaceutical Division of Imperial Chemical Industries (ICI) as a drug candidate. Specifically, preclinical evaluation of the glycine ester of aphidicolin (NSC 303,812) is now complete an clinical trials are scheduled to start at two European centers in early 1987. Of further significance, aphidicolin markedly inhibits the production of progeny retroviruses by interfering with the synthesis of circular DNA. As such aphidicolin may have some efficacy in the area of Acquired Immune Deficiency Syndrome. It is the intent of our program to develop a highly efficient (i.e., short) synthetic strategy to aphidicolin and related analogs. In addition to the above quite specific synthetic goals, a more general underlying and long range aim of this research program is the development of a better understanding of the molecular architecture responsible for the antitumor properties of these and related systems. Thus, as we develop our method of procedure for each of the above synthetic targets, we will also introduce various models systems which will be amenable to construction and subsequent testing, such that in the end we will be able to dissect out the critical structural feature or features responsible for the observed antitumor properties. Once such features are identified, the design of new and possibly more effective antitumor and/or AIDS drugs should be feasible.